Heterosexual contact is the predominant mode of HIV transmission worldwide, accounting for 75-85% of all infections. Interestingly, in North America, where intravenous drug use and homosexual transmission account for over 90% of cases of HIV-1 infection, viral subtype B is predominant; in Thailand, where the epidemic is predominantly heterosexual in nature, subtype E is predominant. This difference in subtype predominance and mode of transmission may be due to the initial introduction of a specific viral subtype into specific subpopulations and the subsequent dissemination following the behavior patterns of that subpopulation. Alternatively, there may be viral factors which cause differences in transmission tropism. A study of serodiscordant couples in drug clinics and sexually transmitted disease (STD) clinics has reported that subtype E virus in Thailand appears to be transmitted heterosexually more easily than subtype B virus. It has also been noted that the risk per contact of female to male transmission of subtype E virus in Thailand appears to be higher than for subtype B virus in the United States. This study aims to determine if the difference in transmissability between HIV-1 subtypes B and E is due to differences in vaginal mucosal and/or Langerhans cell susceptibility to infection with the two clades. To this end, we took vaginal mucosal biopsies from HIV-1 infected female volunteer subjects in Thailand and the United States and performed viral load analysis on these tissues as well as analysis of peripheral blood and other clinical factors. The distribution of CD4+ T-cell counts and plasma viral load was found to be comparable between Thai (subtype E) and American (subtype B) subjects. There was no statistical difference between the mean viral load between the 2 study groups (303,000 copies RNA/ml in the Thai population, versus 287,000 copies/ml in the U.S.). In addition, the peripheral blood mononuclear cell (PBMC) viral DNA and RNA load in Thai subjects was in the range of what has been found for American subjects. Viral DNA and RNA has been amplified from the vaginal mucosal samples. Ongoing work focuses on completing vaginal mucosal tissue viral load analysis, at both the level of whole tissue and in isolated epidermal samples, as well as in situ analysis of fixed tissue samples. We will compare HIV-1 subtypes B and E and ascertain if the differential heterosexual transmission between subtypes B and E is due to local differences in the vaginal mucosa. A better understanding of heterosexual transmission of HIV-1, which accounts for the vast majority of new infections, will hopefully provide useful insight into the design of preventative and therapeutic measures.